Pain
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Mechanical allodynia is pain caused by normally innocuous mechanical stimuli and is a cardinal and intractable symptom of neuropathic pain. Roles of low-threshold mechanoreceptors (LTMRs), including Aβ fibers, in mechanical allodynia have previously been proposed, but the necessity and sufficiency of LTMRs in allodynia have not been fully determined. Recent technological advances have made it possible to achieve subpopulation-specific ablation, silencing or stimulation, and to dissect and elucidate complex neuronal circuitry. ⋯ Whole-cell recording has revealed that optical Aβ stimulation after nerve injury causes excitation of lamina I dorsal horn neurons, which are normally silent by this stimulation. Moreover, Aβ stimulation after nerve injury results in activation of central amygdaloid neurons and produces aversive behaviors. In summary, these findings indicate that optogenetics is a powerful approach for investigating LTMR-derived pain (resembling mechanical allodynia) with sensory and emotional features after nerve injury and for discovering novel and effective drugs to treat neuropathic pain.
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Neuropathic itch is clinically important but has received much less attention as compared to neuropathic pain. In the past decade, itch-specific pathways have been characterized on a cellular and molecular level, but their exact role in the pathophysiology of neuropathic itch is still unclear. Traditionally, mutually exclusive theories for itch such as labeled line, temporal/spatial pattern, or intensity theory have been proposed, and experimental studies in mice mainly favor the specificity theory of itch. ⋯ Rarefication of skin innervation in neuropathy could provide a "spatial contrast" discharge pattern, and axotomy could induce de novo expression of the itch-specific spinal neuropeptide, gastrin-releasing peptide, in primary afferent nociceptors, thereby modulating itch processing in the dorsal horn. Thus, clinical neuropathy may generate itch by changes in the spatial and temporal discharge patterns of nociceptors, hijacking the labeled line processing of itch and abandoning the canonical scheme of mutual exclusive itch theories. Moreover, the overlap between itch and pain symptoms in neuropathy patients complicates direct translation from animal experiments and, on a clinical level, necessitates collaboration between medical specialities, such as dermatologists, anesthesiologists, and neurologists.
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Small families carrying rare mutations, which I call "pointer-kindreds," can teach us important lessons. Here, I provide some examples from the field of pain.
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Numerous studies have examined how alexithymia (difficulty identifying and describing one's emotions and a preference for externally oriented thinking) relates to chronic pain and associated disability. We conducted a systematic review and meta-analysis to summarize individual studies that either assessed alexithymia in individuals with chronic pain vs controls or related alexithymia to pain intensity, physical interference, depression, and anxiety. We searched MEDLINE, Embase, and PsycINFO from inception through June 2017; 77 studies met the criteria (valid assessment of alexithymia in adults or children with any chronic pain condition) and were included in analyses (n = 8019 individuals with chronic pain). ⋯ Secondary meta-analyses of 14 studies that conducted partial correlations that controlled for negative affect-related measures revealed that alexithymia was no longer significantly related to pain intensity or interference. Meta-analysis findings demonstrated that alexithymia is elevated in individuals with chronic pain and related to greater pain intensity and physical interference, although the latter relationships may be accounted for by negative affect. Critical future work is needed that examines alexithymia assessed using non-self-report measures, develops a person-centered perspective on this construct, and identifies how alexithymia is relevant to the assessment and treatment of individuals with chronic pain.